In:
Nucleic Acids Research, Oxford University Press (OUP), Vol. 48, No. 18 ( 2020-10-09), p. 10397-10412
Abstract:
The RNA helicase RIG-I plays a key role in sensing pathogen-derived RNA. Double-stranded RNA structures bearing 5′-tri- or diphosphates are commonly referred to as activating RIG-I ligands. However, endogenous RNA fragments generated during viral infection via RNase L also activate RIG-I. Of note, RNase-digested RNA fragments bear a 5′-hydroxyl group and a 2′,3′-cyclic phosphate. How endogenous RNA fragments activate RIG-I despite the lack of 5′-phosphorylation has not been elucidated. Here we describe an endogenous RIG-I ligand (eRL) that is derived from the internal transcribed spacer 2 region (ITS2) of the 45S ribosomal RNA after partial RNase A digestion in vitro, RNase A protein transfection or RNase L activation. The immunostimulatory property of the eRL is dependent on 2′,3′-cyclic phosphate and its sequence is characterized by a G-quadruplex containing sequence motif mediating guanosine-5′-triphosphate (GTP) binding. In summary, RNase generated self-RNA fragments with 2′,3′-cyclic phosphate function as nucleotide-5′-triphosphate binding aptamers activating RIG-I.
Type of Medium:
Online Resource
ISSN:
0305-1048
,
1362-4962
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2020
detail.hit.zdb_id:
1472175-2
SSG:
12
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